Skip to main content
SpringerLink
Log in

Therapeutic Effect of Venotonics in Chronic Venous Insufficiency

A Meta-Analysis

  • Clinical Use
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Objective: To evaluate, by means of a review of published data, the therapeutic effectiveness of drugs administered orally in the treatment of chronic venous insufficiency.

Data Sources: A computerised literature database, MEDLINE, was used to search for reports written in English, German, North European or Latin-based languages and published between 1980 and 1998. References including the following key words or medical subjects were retrieved: ‘venous insufficiency or varicose veins’ combined with ‘drug therapy’. The Iowa Drug Information Service and the Cochrane Library were used as complementary databases.

Study Selection: Studies were included if they were randomised, double-blind, placebo-controlled clinical trials of at least 4 weeks’ duration in patients receiving oral treatment only.

Data Extraction: Data pertaining to subjective and objective symptoms that were usually reported in the follow-up of patients with chronic venous insufficiency were abstracted independently and blindly by both authors.

Statistical Methods: A qualitative meta-analysis was carried out to assess the quality of the published reports. A quantitative analysis based on changes in subjective and objective symptoms was performed by combining data obtained after using different drugs. Classic standard statistical methods [pooled odds ratio (OR) and 95% confidence intervals (CIs) for subjective symptoms and pooled ‘z’ and ‘p’ for objective symptoms] were employed.

Data Synthesis: In total, 21 reports were analysed. Out of a maximum score of 100 points, these studies averaged 64.4 points. Drug therapy improved heaviness of legs (pooled OR 0.26; CI 0.17 to 0.39; χ 2= 4.04). The results also suggested that drug therapy could produce a decrease in limb perimeter accompanied by a decrease in venous capacity and an increase in venous outflow.

Conclusion: The present analysis permits the conclusion that oral administration of venotonics may improve the heaviness of legs in patients with chronic venous insufficiency. An increase in venous outflow was also suggested by the data obtained.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Madar G, Widmer LK, Zemp E, et al. Varicose veins and chronic venous insufficiency disorder or disease? VASA 1985; 15: 126–34

    Google Scholar 

  2. Evans CJ, Fowkes FGR, Hajivassiliou CA, et al. Epidemiology of varicose veins. Int Angiol 1994; 13: 263–70

    PubMed  CAS  Google Scholar 

  3. Enghofer E, Eisenburger R, Seibel K. Venentonisierende Wirkung und therapeutische Wirksamkeit von rosskastaniensamenextrakt bei der orthostatischen fehlregulation. Therapiewoche 1984; 29: 4360–72

    Google Scholar 

  4. Fischer H. Pflanzliche venentherapeutika. Therapiewoche 1984; 34: 4101–6

    Google Scholar 

  5. Fischer H. Phytotherapie der Venenerkrankungen 1. Zeitsch für Phytother 1985; 6: 33–8

    Google Scholar 

  6. Marshall M. Venenpharmaka — neue Ansatze zur Objektivierung der Therapie-Effekte. Fortschr Med 1984; 102: 772–4

    PubMed  CAS  Google Scholar 

  7. Partsch H, Mostbeck A. Constriction of varicose veins and improvement of venous pumping by dihydroergotamine. VASA 1985; 14: 74–80

    PubMed  CAS  Google Scholar 

  8. Cheatle TR, Scurr JH, Coleridge Smith PD. Drug treatment of chronic venous insufficiency and venous ulceration: a review. J R Soc Med 1991; 84: 354–8

    PubMed  CAS  Google Scholar 

  9. Pathak D, Pathak K, Single AK. Flavonoids as medicinal agents. Recent advances. Fitoterapia 1991; 62: 371–89

    CAS  Google Scholar 

  10. Ferrari PA, Follet M, Clerici G. Treatment of chronic venous diseases with oral glycosaminoglycans: a meta-analysis of double-blind, placebo controlled studies. Curr Ther Res 1994; 55: 1182–91

    Article  Google Scholar 

  11. Hardman J, Limbird L, editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. New York: McGraw Hill, 1996

    Google Scholar 

  12. Anon. Paroven: not much effect in trials [editorial]. Drug Ther Bull 1992; 30: 7-8

  13. Ernst E, Saradeth T, Resch KL. The powerful placebo. Lancet 1991; 337: 611

    Article  PubMed  CAS  Google Scholar 

  14. De Miguel V, Vargas E. Venotónicos en el tratamiento de la insuficiencia venosa crónica: una revisión sistemática. Inform Terap 1997; 21: 33–40

    Google Scholar 

  15. Boada J, Nazco J. Clinical effectiveness of venotonic drugs: a meta-analysis. In: XX Congress of the Spanish Society of Pharmacology; 1996 Sep 18–20; Granada. Meth Find Exp Clin Pharmacol; 18 Suppl. B: 15–8

    CAS  Google Scholar 

  16. Jenicek M. Méta-analyse en Médecine. Paris: Maloine S.A., 1987

    Google Scholar 

  17. Chalmers TC, Smith H, Blackburn R, et al. A method for assessing the quality of randomized control trials. Control Clin Trials 1991; 2: 31–49

    Article  Google Scholar 

  18. Mantel N, Haenzsel W. Statistical aspects of the analysis data from retrospective studies of disease. J Natl Cancer Inst 1959; 22:719–48

    PubMed  CAS  Google Scholar 

  19. Collins R, Langman M. Treatment with histamine H2 antagonists in acute upper gastrointestinal hemorrhage. N Engl J Med 1985; 313: 660–6

    Article  PubMed  CAS  Google Scholar 

  20. Hedges LV, Olkin I. Statistical methods for meta-analysis. New York: Academic Press, 1985

    Google Scholar 

  21. Yusuf S, Peto R, Lewis J, et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985; 27: 335–71

    Article  PubMed  CAS  Google Scholar 

  22. Rosenthal R. Assessing the statistical and social importance of the effects of psychotherapy. J Consult Clin Psychol 1983; 51:4–13

    Article  PubMed  CAS  Google Scholar 

  23. Balmer A, Limoni C. A double blind placebo controlled clinical trial of Venoruton on the symptoms and signs of chronic venous insufficiency. The importance of patient selection. VASA 1980; 9: 1–7

    Google Scholar 

  24. Roeckaerts F, van den Bussche G. Double blind placebo-controlled studies with flunarizine in venous insufficiency. Angiology 1980; 31: 833–45

    Article  PubMed  CAS  Google Scholar 

  25. Allegra C, Pollari G, Criscuolo A, et al. L’estratto di centella asiatica nelle flebopatie degli arti inferiori. Clin Ter 1981; 99: 507–13

    PubMed  CAS  Google Scholar 

  26. Partsch H. Besserung der venösen Insuffizienz durch orales Dihydroergotamin. Med Welt 1981; 32: 1668–71

    PubMed  CAS  Google Scholar 

  27. Biland L, Blättler P, Scheibler P, et al. Zur therapie sogenannt venöser beinbeschwerden. VASA 1982; 11: 53–8

    PubMed  CAS  Google Scholar 

  28. Hachen HJ, Lorenz P. Double-blind clinical and plethysmographic study of calcium dobesilate in patients with peripheral microvascular disorders. Angiology 1982; 33: 480–7

    Article  PubMed  CAS  Google Scholar 

  29. Lange A, Paul V. Wirksamkeit von Vasoc auf die Symptomatik der venösen insuffizienz. Med Welt 1982; 33: 1132–5

    PubMed  CAS  Google Scholar 

  30. Spinella G, Majorana M. Tribenoside nel trattamento delia malattia varicosa degli arti inferiori: ricerca clinica controllata. Clin Ter 1982; 101: 587–601

    PubMed  CAS  Google Scholar 

  31. Brami C, Nguyen K, Morere M, et al. Etude controlée en double aveugle du Vasobral versus placebo dans l’insuffisance veineuse chronique. Angeiologie 1983; 35: 281–3

    Google Scholar 

  32. Bergqvist D, Hallbook T. Die Wirkung von O-(β-hydroxyethyl)-rutosiden auf die Symptomatik bei Patienten mit chronisch-venöser Insuffizienz in einer schwedischen Gemeinde-Ein Doppelblindversuch. In: Voelter W and Jung G, editors. O-(β-hydroxyethyl)-rutoside, neue ergebnisse im Experiment und Klinik. New York: Springer Verlag; 1983: 169–78

    Chapter  Google Scholar 

  33. Languillat N, Baillet J. Effets pharmacologiques du Chromocarbe diéthylamine sur la circulation veineuse des membres inférieurs appréciée par l’exploration au xénon 133. Gaz Med 1983; 90: 3398–402

    Google Scholar 

  34. Pulvertaft TB. General practice treatment of symptoms of venous insufficiency with oxerutins. VASA 1983; 12: 373–6

    PubMed  CAS  Google Scholar 

  35. Le Devehat C, Lemoine A, Roux E, et al. Aspects clinique et hemodynamique de cyclo 3 dans l’insuffisance veineuse. Angeiologie 1984; 36: 119–22

    Google Scholar 

  36. Spano VS. Étude clinique du chromocarbe diéthylamine dans le traitaient de l’insuffisance veineuse périphérique. Ann Cardiol Angeiol 1984; 33: 485–7

    CAS  Google Scholar 

  37. Sentou Y, Bernard-Fernier MF, Demarez JP, et al. Symptomatologie et plethysmographie: parallelisme des resultats obtenus lors d’un traitaient par cyclo 3 de patients porteuses d’une insuffisance veineuse chronique (etude en double insu contre placebo). Gaz Med 1985; 92: 73–7

    Google Scholar 

  38. De Donato G, Sangiuolo, P. Valutazione strumentale degli effetti del mesoglicano in pazienti flebopatici. Minn Med 1986; 77: 1927–31

    Google Scholar 

  39. Rudofsky G. Odemprotektive Wirkung und klinische Wirksamkeit von rosskastaniensamenextrakt im doppelblindversuch. Fortschr Med 1986; 104; 47–8

    Google Scholar 

  40. Nocker W, Diebschlag W. An investigation of dosage effects with drinking solutions of O-betahydroxyethyl-rutosides. VASA 1987; 16: 365–9

    PubMed  CAS  Google Scholar 

  41. Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiology 1987; 38: 46–50

    Article  PubMed  CAS  Google Scholar 

  42. Capelli R, Nicora M, Di Perri T. Use of extract of Ruscus aculeatus in venous disease in the lower limbs. Drugs Exp Clin Res 1988; 14:277–83

    Google Scholar 

  43. Casley-Smith JR. A double blind trial of calcium dobesilate in chronic venous insufficiency. Angiology 1988; 39: 853–7

    Article  PubMed  CAS  Google Scholar 

  44. Laurent R, Gilly R, Frileux C. Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg. Int Angiol 1988; 7 Suppl. 2: 39–43

    PubMed  CAS  Google Scholar 

  45. Burnand KG, Powell S, Bishop C, et al. Effect of paroven on skin oxygenation in patients with varicose veins. Phlebology 1989; 4: 15–22

    Google Scholar 

  46. De Jongste AB, Jonker JJ, Huisman MV, et al. A double blind three center clinical trial on the short-term efficacy of O-(beta-hydroxyethyl)-rutosides in patients with post-thrombotic syndrome. Thromb Haemost 1989; 62: 826–9

    Google Scholar 

  47. Nocker W, Diebschlag W, Lehmacher W Three-month, randomised, double-blind, dose-response study with O-(beta-hydroxyethyl)-rutosides drinking solution. VASA 1989; 18: 235–8

    PubMed  CAS  Google Scholar 

  48. Tsouderos YAre the phlebotonic properties shown in clinical pharmacology predictive of a therapeutic benefit in chronic venous insufficiency? Our experience with Daflon 500 mg. Int Angiol 1989; 8(4 Suppl.): 53–9

  49. Neumann HAM, van den Broek MJTB. Evaluation of O-(beta-hydroxyethyl)-rutosides in chronic venous insufficiency by means of non-invasive techniques. Phlebology 1990; 5 Suppl. 1: 13–21

    Google Scholar 

  50. Pecchi S, De Franco V, Damiani P, et al. Calcium dobesilate in the treatment of primary venous insufficiency of the lower limbs. A controlled clinical study. Clin Ter 1990; 32: 409–17

    Google Scholar 

  51. Widmer L, Biland L, Barras JP. Doxium 500 in chronic venous insufficiency: a double-blind placebo-controlled multicentre study. Int Angiol 1990; 9: 105–10

    PubMed  CAS  Google Scholar 

  52. Domínguez C, Brautigam I, González E, et al. Therapeutic effect of hydrosmin on chronic venous insufficiency of lower limbs. Curr Med Res Opin 1992; 12: 623–30

    Article  PubMed  Google Scholar 

  53. Fermoso J, Legido AG, del Pino J, et al. Therapeutic value of hidrosmin in the treatment of venous disorders of the lower limbs. Current Ther Res 1992; 52: 124–34

    Article  Google Scholar 

  54. Pedersen FM, Hamberg O, Sorensen MD, et al. O-(beta-hydroxyetyl)-rutosids (Venoruton) effekt pa symptom-givende kronisk venos insufficiens i underekstremiteterne. UgeskrLaeger 1992; 154: 2561–3

    CAS  Google Scholar 

  55. Corsi C, Giordano S, Marrapodi F, et al. Effectiveness of sulfomucopolysaccharide in the treatment of chronic venous insufficiency. Curr Ther Res 1993; 54: 35–43

    Article  Google Scholar 

  56. Binaghi F, Fronteddu PF. Valutiazione dei parametri ossimetrici e doppler sonografici nei pazienti con insufficienza venosa cronica. Clin Ter 1994; 144: 293–9

    PubMed  CAS  Google Scholar 

  57. MacLennan WJ, Wilson J, Rattenhuber V, et al. Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability. Gerontology 1994; 40: 45–52

    Article  PubMed  CAS  Google Scholar 

  58. Schuller-Petrovic S, Wolzt M, Böhler K, et al. Studies on the effect of short term oral dihydroergotamine and troxerutin in patients with varicose veins. Clin Pharmacol Ther 1994; 4: 452–9

    Article  Google Scholar 

  59. Ihme N, Kiesewetter H, Jung F, et al. Leg oedema protection from a buckwheat herb tea patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial. Eur J Clin Pharmacol 1996; 50: 443–7

    Article  PubMed  CAS  Google Scholar 

  60. Launois R, Reboul-Marty J, Henry B. Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ). Qual Life Res 1996; 5: 539–50

    Article  PubMed  CAS  Google Scholar 

  61. Preziosi P, Galan P, Aissa M, et al. Prevalence of venous insufficiency in French adults of the SUVIMAX cohort. Supplementation en Vitamines et Mineraux AntioXydants. Int Angiol 1999; 18: 171–5

    PubMed  Google Scholar 

  62. De Castro M. Chronic venous insufficiency of the lower limbs and its socio-economic significance. Int Angiol 1991; 10: 152–7

    Google Scholar 

  63. Boada J, Nazco J, Martin JG, et al. Overview of clinical trials of hidrosmin in the treatment of chronic venous insufficiency of the lower limbs. Current Ther Res 1992; 52: 40–5

    Article  Google Scholar 

  64. Poynard T, Valterio C. Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency. VASA 1994; 23: 244–50

    PubMed  CAS  Google Scholar 

  65. Pittler MH, Ernst E. Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review. Arch Dermatol 1998; 134: 1356–60

    Article  PubMed  CAS  Google Scholar 

  66. Geroulakos G, Nicolaides AN. Controlled studies of Daflon 50 mg in chronic venous insufficiency. Angiology 1994; 45: 549–53

    PubMed  CAS  Google Scholar 

  67. Barthel W. Venentonisierender effekt, pharmakokinetic und unerwünchste Wirkungen von dihydroergotamin. Z Gesamte Inn Med 1984; 39: 417–28

    PubMed  CAS  Google Scholar 

  68. Enghofer E, Seibel K, Hammersen F. Die antiexsudative Wirkung von roβkastaniensamenextrakt. Therapiewoche 1984; 34: 4131–44

    Google Scholar 

  69. Hitzenberger G. Die therapeutische Wirksamkeit des ross-kastaniensamenextraktes. Wien Med Wochenschr 1989 15; 139: 385–9

    Google Scholar 

  70. Regenthal R, Voigt H, Grossmann K. Möglichkeiten und grenzen der pharmakotherapie der chronisch-venösen insuffizienz. Z Gesamte Inn Med 1990; 45: 108–13

    PubMed  CAS  Google Scholar 

  71. Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs 1992; 44: 1013–32

    Article  PubMed  CAS  Google Scholar 

  72. Angehrn F. Efficacy and safety of calcium dobesilate in patients with chronic venous insufficiency: an open label study. Current Ther Res 1995; 56: 346–57

    Article  Google Scholar 

  73. Meyer OC, Boccalon H, Janbon C, et al. Characteristics of chronic venous insufficiency in 895 patients followed in general practice. Int Angiol 1997; 16: 226–34

    Google Scholar 

  74. Allart JC. La dihydroergotamine a liberation programmée en practique phlebologique courente et de son interet dans les cas ayant résisté a d’autre therapeutiques. Phlebologie 1980; 33: 201–6

    PubMed  CAS  Google Scholar 

  75. Gounon P. Etude de la permeabilité capillaire dans l’evaluation objective d’un veinotonique. Phlebology 1980; 33: 569–74

    CAS  Google Scholar 

  76. Elbaz C. Etude clinique de l’efficacité de cirkan en phlebologie. Phlebology 1980; 33: 379–90

    CAS  Google Scholar 

  77. Krief I. Action du Daflon sur la douleur, les cramps et l’oedeme en pathologie veineuse. Lille Med 1980; 25: 470–2

    PubMed  CAS  Google Scholar 

  78. Mayall RC, Mayall AC, Brito AC, et al. Daflon dans la pathologie veineuse périphérique. Angeiologie 1980; 32: 329–31

    Google Scholar 

  79. Rocco P. Valutazione dell’eficacia delia terapia con farmaci flebotropi mediante teletermografia dinamica. Minerva Med 1980; 71: 2071–8

    PubMed  CAS  Google Scholar 

  80. Grismondi GL. Contributo al trattamento delie flebopatie da stasi in gravidanza. Minerva Ginecol 1981; 33: 221–30

    PubMed  CAS  Google Scholar 

  81. Barthel W, Grossmann K. A comparative plethysmographic study of the venoconstrictor effect of dihydroergotamine and dihydroergotoxine on the deep veins of the calf in healthy subjects and patients suffering from varicosis. Int J Clin Pharmacol Ther Toxicol 1982; 20: 458–64

    PubMed  CAS  Google Scholar 

  82. Klemm J. Stromungsgeschwindigkeit von blut in varikösen venen der unterenextremitaten. EinfluB eines venentherapeutikums (Venostasin). MMW Munch Med Wochenschr 1982; 124: 579–82

    PubMed  CAS  Google Scholar 

  83. Schander K, Heinemann-Quirmbach C. Plethysmographische Untersuchungen zur diagnostik von venenerkrankungen. Phlebol Proktol 1982; 1: 22–9

    Google Scholar 

  84. Wiemers U, Voigt H, Voigt T, et al. Chronic venous insufficiency. Mechanical or drug compression? Z Gesamte Inn Med 1982; 37: 29–31

    PubMed  CAS  Google Scholar 

  85. Pedrini L, Cifiello B. Modificazioni delie funzionalitá venose rilevate dopo trattanmento farmacologico. Studio pletismografico. Clin Ter 1984; 106: 271–7

    Google Scholar 

  86. Spano V, Mancini A, Slatopolsky-Cantis M. Evaluation of the venotropic effect of chromocarb diethylamine in patients with varicose veins. Ann Cardiol Angiol 1984; 33: 407–10

    CAS  Google Scholar 

  87. Allegra C, Bonifacio M, Riccioni C, et al. Mesoglicani e flebopatie. Contributo clinico-esperimentale. Minerva Med 1986; 77: 1887–92

    PubMed  CAS  Google Scholar 

  88. Bracale GC, Selvetella L, Mirabile E. L’attivitá terapeutica del mesoglicano per os nelle flebopatie. Minerva Med 1986; 77: 1919–25

    PubMed  CAS  Google Scholar 

  89. Cianfanelli G, Borreani B, Zepponi E, et al. Il ruolo del mesoglicano nel trattamento delle flebopatie di interesse chirurgico. Minerva Med 1986: 77: 1943–4

    PubMed  CAS  Google Scholar 

  90. Mangoni N, Righi D, Lucente E, et al. Risultati delia nostra esperienza sull’impiego del mesoglicano nella terapia delle flebopatie acute e croniche degli arti inferiori. Minerva Med 1986; 77: 1903–8

    PubMed  CAS  Google Scholar 

  91. Petruzzellis V, Velon A. Rilievi clinici e ossimetrici cutanei sull’attivita del mesoglicano somministrato per os (100 mg/die), nelle dermatiti flebopatiche. Minerva Med 1986; 77: 1911–3

    PubMed  CAS  Google Scholar 

  92. Signorelli S, Ferrara M, Tornetta D, et al. Synthetic diosmin in the therapy of venous diseases. Panminerva Med 1987; 29: 165–7

    PubMed  CAS  Google Scholar 

  93. Guillot B, Guilhou JJ, Champvallins M, et al. A long term treatment with a venotopic drug. Int Angiol 1989; 8 Suppl. 4: 67–71

    PubMed  CAS  Google Scholar 

  94. Sangrigoli V, Carra G, Lazzara N, et al. Mesoglycan in acute and chronic venous insufficiency of the legs. Clin Ter 1989; 129: 207–9

    PubMed  CAS  Google Scholar 

  95. Wenzel E, Birkel L, Scheffler P, et al. Control of therapy with microcirculatory and phlebotropically active drugs in patients with congenital and acquired venous insufficiency. Int Angiol 1989; 8: 41–6

    PubMed  CAS  Google Scholar 

  96. Languillat N, Ladure Ph, Magnan N, et al. Exploration fonctionelle de la vitesse circulatoire veineuse grace au xenon 133. Gaz Med 1992; 99: 2–7

    Google Scholar 

  97. Baricevic J. Does calcium dobesilate (doxium) improve the microcirculation and the musculovenous pump in patients with varicose veins? VASA 1980; 9: 240–5

    PubMed  CAS  Google Scholar 

  98. Berson I, Geiser JD. Etude comparative ouverte entre deux phlebotropes chez deux groupes repartis au hasard. Schweiz Rundsc Med Prax 1980; 69: 1244–6

    Google Scholar 

  99. Royer RJ, Schmidt CL. Intéret de la pléthysmographie gazeuse pour l’appréciation des effets veinotropes des médicaments. Sem Hop 1981; 57: 2009–13

    PubMed  CAS  Google Scholar 

  100. Marastoni F, Baldo A, Redaelli G, et al. L’estratto di Centella asiatica nella patologia venosa degli arti inferiori e sua valutazione versus tribenoside. Minerva Cardioangiol 1982; 30: 201–7

    PubMed  CAS  Google Scholar 

  101. De Caprio M, Vinci L, Guimetti D, et al. Esperienze cliniche con un farmaco vasoprotettore nel trattamento dei problemi venosi degli arti inferiori. Clin Ter 1982; 101: 497–508

    Google Scholar 

  102. Petruzzellis V, Velon A. Sull’attivitá terapeutica del mesoglicano, somministrato per os, neltrattamento farmacologico delia sindrome varicosa e delle sue complicanze. Minerva Med 1985; 76: 543–8

    PubMed  CAS  Google Scholar 

  103. Schmidt C, Demage G, Kohler F, et al. Etude pléthysmographique et pharmacocinetique d’un phlébotrope: le flavodate disodique. Therapie 1985; 40: 221–4

    PubMed  CAS  Google Scholar 

  104. Cospite M, Milio G, Ferrara F. L’azione del mesoglicano solfato nella varicosi primitiva e nella sindrome post-trombotica. Minerva Med 1986; 77: 1893–8

    PubMed  CAS  Google Scholar 

  105. Duchene Marullaz P, Amiel M, Barbe R. Evaluation of the clinical pharmacological activity of a phlebotonic agent. Application to the study of Daflon 500 mg. Int Angiol 1988; 7(2 Suppl.): 25–32

    Google Scholar 

  106. Androulakis G, Panoysis PA. Plethysmographic confirmation of the beneficial effect of calcium dobesilate in primary varicose veins. Angiology 1989; 40: 1–4

    Article  PubMed  CAS  Google Scholar 

  107. Cospite N, Dominici A. Double blind study of the pharmacodynamic and clinical activities of 5862 SE in venous insufficiency. Advantages of the new micronized form. Int Angiol 1989; 8(4 Suppl.): 61–5

    PubMed  CAS  Google Scholar 

  108. Sannazzari P. Low molecular weight heparin in the symptomatic treatment of chronic venous insufficiency. Controlled double blind study vs calcium heparin. Panminerva Medica 1989; 31: 127–33

    PubMed  CAS  Google Scholar 

  109. De Anna D, Mari F, Intini F, et al. Effetti delia terapia con aminoaftona sulla stasi venosa e linfaticacronica. Minerva Cardioangiol 1989; 37: 251–4

    Google Scholar 

  110. Honorato J, Arcas R. A double blind study comparing the clinical efficacy of the preparation F117 (hidrosmin) versus diosmin in the treatment of patients with peripheral venous disorders. Rev Med Univ Navarra 1990; 34: 77–9

    Google Scholar 

  111. Monreal M, Callejas JM, Martorell A, et al. A prospective study of the long-term efficacy of two different venoactive drugs in patients with post-thrombotic syndrome. Phlebology 1994; 9: 37–40

    Google Scholar 

  112. Cesarone MR, Laurora G, De Sanctis MT, et al. The microcirculatory activity of Centella asiatica in venous insufficiency. A double-blind study. Minerva Cardioangiol 1994; 42: 299–304

    PubMed  CAS  Google Scholar 

  113. Lee RE, Bykady G, Ritschel W. Inhibition of prostaglandin biosynthesis by coumarin, 4-hydroxycoumarin and 7-hydroxycoumarin. Arzneimittelforschung 1981; 4: 640–2

    Google Scholar 

  114. Radtke H, Kiesewettrer H, Schneider R. Die rheologische Wirksamkeit von cumarin und troxerutin. Therapiewoche 1983; 49: 6662–6

    Google Scholar 

  115. Anon. Rosskastanie hemmt lysosomale enzymaktivität — Terapieerfolge bei varikosis [editorial]. Fortschr Med 1983; 101: 1684

  116. Muller-Schweinitzer E. Pharmacological actions of the main metabolites of dihydroergotamine. Eur J Clin Pharmacol 1984; 26: 699–705

    Article  PubMed  CAS  Google Scholar 

  117. Muller-Schweinitzer E. Alpha-adrenoceptors, 5-hydroxytryptamine receptors and the action of dihydroergotamine in human venous preparations obtained during saphenectomy procedures for varicose veins. Naunyn Schmiedebergs Arch Pharmacol 1984; 327: 299–303

    Article  PubMed  CAS  Google Scholar 

  118. Sinzinger H, Fitscher P. Prostacyclin (PGI2) contracts normal and varicose human saphenous veins. VASA 1984; 13: 228–30

    PubMed  CAS  Google Scholar 

  119. Araujo D, Gulati O, Osswald W. Effects of two venotropic drugs on inactivation and O-methylation of catecholamines in an isolated canine vein. Arch Int Pharmacodyn Ther 1985; 217: 193–202

    Google Scholar 

  120. Casley-Smith JR, Casley-Smith JuR. The effects of calcium dobesilate on acute lymphedema (with and without macrophagues) and burn edema. Lymphology 1985; 18: 37–45

    PubMed  CAS  Google Scholar 

  121. Behar A, Lagrue G, Cohen-Boulakia F, et al. Capillary filtration in idiopathic cyclic edema. Effects of Daflon 500 mg. Nuklear Medizin 1988; 27: 105–7

    CAS  Google Scholar 

  122. Blumberg S, Clough G, Michel Ch. Effects of hydroxyethyl rutosides upon the permeability of single capillaries in the frog mesentery. Br J Pharmacol 1989; 96: 913–9

    Article  PubMed  CAS  Google Scholar 

  123. Quintana A, Raczka E. Efecto de la hidrosmina sobre la circulación sanguínea regional en la rata. Drugs Today 1988; 24 Suppl. 7: 27–33

    Google Scholar 

  124. Bouskela E, Cyrino FZ, Marcelon G. Possible mechanisms for the venular constriction elicited by Ruscus extract on hamster cheek pouch. J Cardiovasc Pharmacol 1994; 24: 165–70

    Article  PubMed  CAS  Google Scholar 

  125. Savineau JP, Marthan R. Diosmin-induced increase in sensitivity to Ca2+ of the smooth muscle contractile apparatus in the rat isolated femoral vein. Br J Pharmacol 1994; 111: 978–80

    Article  PubMed  CAS  Google Scholar 

  126. Bouskela E, Cyrino FZ, Bougaret S. Effects of Cyclo 3 Fort on microvascular reactivity and the venoarteriolar reflex in diabetic hamsters. Clin Hemorheol Microcirc 1997; 17: 351–6

    PubMed  CAS  Google Scholar 

  127. Coleridge Smith PH. Noninvasive venous investigation. Vascular Med Rev 1990; 1: 139–66

    Article  Google Scholar 

  128. Franco A, Carpentier P. Methods for studying vasoactive drugs in arteriopathy of the leg and chronic venous insufficiency. Arch Mal Coeur 1990; 83, 79–8

    PubMed  Google Scholar 

  129. Felix W. Pharmacological models for the investigation of venotropic drugs. Int Angiol 1984; 3(1 Suppl.): 53–7

    Google Scholar 

  130. Unkauf M, Rehn D, Klinger J, et al. Investigation of the efficacy of oxerutins compared to placebo in patients with chronic venous insufficiency treated with compression stockings. Arzneimittelforschung 1996; 46: 478–82

    PubMed  CAS  Google Scholar 

  131. Renton S, Leon M, Belcaro G, et al. The effect of hydroxyethylrutosides on capillary filtration in moderate venous hypertension: a double blind study. Int Angiol 1994 Sep; 13(3): 259–62

    PubMed  CAS  Google Scholar 

  132. Le Devehat C, Khodabandehlou T, Vimeux M, et al. Evaluation of haemorheological and microcirculatory disturbances in chronic venous insufficiency: activity of Daflon 500 mg. Int J Microcirc Clin Exp 1997; 17 Suppl. 1: 27–33

    Google Scholar 

  133. Janssens D, Michiels C, Guillaume G, et al. Increase in circulating endothelial cells in patients with primary chronic venous insufficiency: protective effect of Ginkor Fort in a randomized double-blind, placebo-controlled clinical trial. J Cardiovasc Pharmacol 1999; 33: 7–11

    Article  PubMed  CAS  Google Scholar 

  134. Diehm C, Trampisch HJ, Lange S, et al. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet 1996; 347: 292–4

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Pharmacology Unit, University Hospital, University of La Laguna, Tenerife, Canary Islands, Spain

    José N. Boada

  2. Hospital Pharmacy, University Hospital, University of La Laguna, Tenerife, Canary Islands, Spain

    Gloria J. Nazco

Authors
  1. José N. Boada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gloria J. Nazco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José N. Boada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boada, J.N., Nazco, G.J. Therapeutic Effect of Venotonics in Chronic Venous Insufficiency. Clin. Drug Investig. 18, 413–432 (1999). https://doi.org/10.2165/00044011-199918060-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-199918060-00001

Keywords

Search

Navigation